Targeted delivery of therapeutics is highly desirable in many medical and veterinary applications. The ability to safely and effectively deliver a therapeutic to a specific location would enable administration of the therapeutic or therapeutics directly to the site of treatment while minimizing any possible side effects associated with systemic delivery of the drug.
Site-specific delivery of a therapeutic or therapeutics is desirable for the treatment of many different conditions, including, for example, the treatment of cancers; cardiovascular diseases; vascular conditions; orthopedic disorders; dental disorders; wounds; autoimmune diseases, such as, e.g., rheumatoid arthritis; gastrointestinal disorders; and even for the targeted delivery of proteins and nucleic acid sequences. Furthermore, medical and veterinary devices, including stents, such as, e.g., coronary vascular stents and peripheral vascular stents; vascular grafts; orthopedic implants, such as, for example, hip and knee implants; devices used in surgical applications and wound healing, such as, e.g., sutures, surgical meshes, bandages, and other mechanical wound closure products; and other types of medical and veterinary devices implanted in the body of humans and animals, frequently induce or are associated with inflammation, swelling, infection, hyperproliferation of adjacent tissues, formation of a capsule or granuloma or fibroma surrounding the implant (also known as the foreign body response), and/or pain in the recipient. Devices and methods that reduce these and other pathological responses are desirable to increase the effectiveness and safety of the implanted medical or veterinary device.
One form of drug delivery involves the use of polymers. The use of polymers for drug delivery began in the 1960s with controlled-release oral formulations that involved coating drug tablets, particles or molecules with non-therapeutic biodegradable polymer materials that break down to release the encoated drug. Since that time, polymers containing therapeutics that are admixed or pendant to the polymer backbone have been developed. In the admixture approach, therapeutics are mixed with the polymers before the polymers harden or gel. In the pendant approach, therapeutics are attached to the polymer backbones, by using linkages such as, e.g., enzymatic, chemical, covalent or electrostatic linkages. Unfortunately, such types of biodegradable polymer drug delivery systems are undesirable due to characteristics such as induction of inflammation and/or host response at the site of delivery, low and/or unpredictable potency, unpredictable breakdown products, non-zero-order release rates and burst effects, that is, initial spikes of drug delivery.
In the case of medical and veterinary devices, it is desirable to coat the devices with biocompatible polymer coatings or other surface technologies to reduce inflammation, swelling, infection, hyperproliferation of adjacent tissues, foreign body response and/or pain. Such coatings and surface technologies to date have typically been non-biodegradable, due to the highly inflammatory and unpredicatable nature of the biodegradable polymer coatings described above. Devices coated with a non-biodegradable coating are disadvantageous because the polymers can fatigue over time and delaminate, which could have catastrophic results in certain situations, such as, e.g. in the case of a coated stent that suffers a delamination event as the stent cycles through many heartbeats in a coronary artery. Therefore, it is clear that devices coated with a coating that degrades leaving a bare device, such as, for example, a biodegradable polymer-coated stent, wherein the coating erodes and leaves a bare metal stent, is desirable. Other detrimental side effects associated with biocompatible polymer coatings and surface technologies include, for example, inflexibility, complexity, loading capacity and duration of delivery.
As such, it is clear that there remains a need in the art for medical devices, pharmaceutical compositions and methods of treatment comprising biodegradable polymers that avoid the disadvantages discussed above.